Sunday, March 31, 2019

Life as you know it....

Prof Ron Davis, world renowned scientist, tells you why you should all be afraid of CFS/ME. It could happen to you. "Your life as you know it, will be over"... take notice. Share this post. We need donations to find a cause and treatments

Monday, March 25, 2019

Meta-Analysis Shows Blunted Heart Rate Contributes to Activity Intolerance in People with ME

Meta-Analysis Shows Blunted Heart Rate Contributes to Activity
Intolerance in People with ME

March 23, 2019
By #MEAction

The Workwell Foundation issued the press release below about its
meta-analysis of 20 years of studies that shows "overwhelming
evidence" of chronotropic incompetence in people with ME/CFS, which
contributes to activity intolerance in people with myalgic
encephalomyelitis (ME).

A normal response to exercise is an increase in heart rate. Failure of
the heart to keep pace with an increase in demand is called
chronotropic incompetence (CI), a disabling condition that causes
activity intolerance and often leads to poor health outcomes.
According to a new meta-analysis from researchers at Workwell
Foundation and the University of the Pacific, CI is commonly found in
people with ME/CFS, a complex neuroimmune disease.

The meta-analysis, published recently in Frontiers in Pediatrics, drew
on 20 years of studies involving 1- and 2-day cardiopulmonary exercise
testing (CPET). When comparing heart rate data between ME/CFS patients
and matched controls, the authors asked if chronotropic incompetence
contributes to the activity intolerance that underscores this disease.

They found overwhelming evidence of CI in ME/CFS patients, including
both men and women, relative to healthy subjects. In a finding unique
to this disease, the study showed that the heart rate response was
even lower on the second day of repeat exercise testing at both peak
and sub-peak levels, putting the oxygen costs of even simple
activities above a safe heart rate threshold for many.

The magnitude of CI also depended on disease severity, with the most
severe patients experiencing even greater differences between actual
and predicted maximum heart rate.

According to Workwell Foundation, CI can make a bad situation worse. A
blunted heart rate in response to exercise could exacerbate the
already low oxygen consumption found in this disease and further limit
levels of activity. CI further compounds post-exertional malaise
(PEM), a worsening of symptoms in response to activity.

The authors hypothesize that an abnormal heart rate response to
exercise is likely due to impaired autonomic regulation of the heart.
They suggest new research directions that should be explored to better
understand what drives the patterns discovered in this paper.

These findings send an important message to health care providers and
patients trying to manage their illness through pacing activities.
Pacing plans based on age-predicted heart rate thresholds should be
viewed with caution because the chronotropic response is impaired in
people with ME/CFS.

The full chronotropic incompetence study titled, "Chronotropic
incompetence: an overlooked determinant of symptoms and activity
limitation in myalgic encephalomyelitis/chronic fatigue syndrome," is
available online in the open-access journal Frontiers in Pediatrics.

Workwell Foundation a fiscally-sponsored program of United Charitable,

a registered 501c3 organization.

*  *  *

If you would like more information about this topic, or to schedule an
interview with Staci Stevens, please contact her at 209.599.7194 or

Sunday, March 24, 2019

"M.E. Patients and the Researchers that Silence Them"

"M.E. Patients and the Researchers that Silence Them" (March 19)


Quite simply, what I, and patients like me want, is a commitment to
biomedical research funding, an awareness among doctors that Graded
Exercise Therapy, in particular, harms our chances of recovery, and
for the stranglehold of psychiatric funding to end. We are not
rabble-rousers, and nor are we anti-science; in fact, we are patently
far more committed to scientific enquiry than the psychiatrists
currently rubbishing us in the press. But we are also unwell, unheard,
and unable to move forward with our lives until these attitudes

As Merryn Crofts mother says:

"More knowledge, education and awareness is desperately needed to stop
the stigma, increase research, and stop the continued suffering of
thousands of people with ME.

"My daughter did not die of 'fatigue'. She died due to multi-systemic
neurological M.E. and change needs to happen — now."

Saturday, December 8, 2018

Cardiac abnormalities in ME/CFS not due to deconditioning

MEA Summary Review: Cardiac abnormalities in ME/CFS not due to deconditioning


MEA Summary Review: Cardiac abnormalities in ME/CFS not due to
deconditioning | 26 November 2018

Charlotte Stephens, Research Correspondent, ME Association.


Click to download our 7-page summary review.

Linda van Campen and Frans Visser from the Netherlands have just
published a study
that examined stroke volume and cardiac output in ME/CFS. It confirmed
earlier findings from a smaller study that changes occurred in these
two key cardiac measures despite normal tilt-table results (Timmers et
al., 2002).

Both studies found reduced cardiac output and stroke volumes during a
tilt table test in ME/CFS patients compared to healthy controls.
However, these patients had normal tilt table results, meaning their
heart rate and blood pressure did not change significantly enough to
be diagnosed with orthostatic intolerance.

The authors of the earlier study suggested that these findings were
due to deconditioning, but in this new, larger study, Van Campen and
Visser showed they were not as they found no difference in results
between different disease severities.

If it were a case of deconditioning, the cardiac measurements would be
worse in the more severely affected compared to the mild, as they have
poorer physical functioning.

What made this study better than the previous one?

Much larger patient cohort. The previous study tested 26 ME/CFS
patients, whereas this current study involved 150 ME/CFS patients.
Improved method of measuring cardiac parameters. The reliability of
the previous study's method (pulse contour analysis) is questionable,
whereas the current study used a validated technique (suprasternal
aortic Doppler echography) (van Geldorp et al., 2011).
The latest study compared results across illness severities. This
revealed that the cardiac abnormalities could not be due to

What were the two key measures found to be different?

Cardiac output = The volume of blood pumped by the heart per minute.

Stroke Volume = The volume of blood pumped by the left ventricle of
the heart per heartbeat.

Both of these measures usually decrease upon standing. However, they
were found to decrease more in the patients with ME/CFS, compared to
the healthy controls.



This research review is available for free.


Click to read online or to download.


The MEA Ramsay Research Fund Christmas Appeal

We want to invest in more research in 2019 and we need you help to do it.

If you would like to support our Christmas Appeal, then please:

Donate online via our JustGiving page
Donate by card over the phone to head office (01280 818964).
Donate by cheque payable to The ME Association (with a note saying
that it is for the Christmas Appeal) to ME Association, 7 Apollo
Office Court, Radclive Road, Gawcott, Buckinghamshire, MK18 4DF.

For more information please visit our Christmas Appeal webpage
<> . And if you have any
questions get in touch with Helen Hyland or Head Office. Thank you.

* * *

I once led a doctor by the hand through no, you would not become that deconditioned that quickly; it would take months to become so deconditioned that you can't walk two blocks.  

And half a minute later, he was back to insisting that I was "just deconditioned" and needed to exercise my way back to health.

So I walked him through it again, that in a matter of days I went from being able to walk 5 miles a day to barely making it from the bus stop to my desk, and then having to rest for an hour before I could do any work.  Again, he agreed that it would take months to get that out of shape, and again he promptly reverted to telling me that there was nothing physically wrong other than I'd let myself become deconditioned and would be back to normal in a jiffy if I just pushed myself to exercise a little more each day.

Another Warrior Gone

In Memoriam Jan van Roijen 
June 11, 1937 - December 5, 2018

Today the utterly sad news of the death of Dutch ME-patient Jan van Roijen reached us. He died Wednesday night in a nursing home where he spent the last few months of his life of 81 years.

Jan was known throughout the ME-world for his detailed knowledge of ME in all its aspects, which he shared with the global community through his bulletin Help ME Circle, for his generosity and kindness and for his humour, even in spite of his being so severely ill. Until very short before his death he lived in his apartment at the second storey of a monumental building in the very centre of Amsterdam.

Jan was a top-actor who performed with wellknown actors like Willeke van Ammelroy and other famous Dutch actors on stage when he fell seriously ill. One by one he lost all his friends and was visited by only a handful of friends during the last years of his life.

Rest in peace, dear friend…

Sunday, November 18, 2018

Wednesday, October 24, 2018

Symposium on the Molecular Basis of ME/CFS

At the three-day Working Group Meeting and Community Symposium on the
Molecular Basis of ME/CFS at Stanford University, sponsored by OMF, so
much scientific progress was evident. We are clearly progressing from
just data gathering to formulating new hypotheses as to the causes of
symptoms and even a possible cause of the disease. The buzz of hope
was palpable!

The Working Group Meeting brought together over 50 researchers from
around the world. Ronald W. Davis, PhD, OMF Scientific Advisory Board
Director, invited world-renowned researchers who were open to
collaboration and sharing unpublished data. As Dr. Davis said, "I
invited brilliant people with a high intellect to arrogance ratio who
are working on ME/CFS at the molecular level. The knowledge shared
this year was considerably greater than last year. The excitement to
begin new collaborations was intense. They were so engaged in planning
out their new collaborations that it was difficult to start the next
session. It felt like an explosion of ideas."

The Community Symposium gathered together patients, caregivers,
clinicians, and researchers. We welcomed nearly 300 participants at
Stanford and over 4,800 Livestream participants. The day was filled
with excellent research reports, the warm embrace of community, and
shared tremendous hope.

I want to thank the researchers for their dedication and hard work,
and everyone involved in this great event who made it such a success.
Thank you also to all the donors who made this important work
possible. Without you this progress couldn't have happened.

Below is a summary of the Community Symposium prepared by Christopher
Armstrong, PhD.

With hope for all,

Linda Tannenbaum
Founder & CEO/President


Second Annual Community Symposium on the Molecular Basis of ME/CFS Summary
By Christopher Armstrong, PhD

During the last week of September, a 3-day Working Group Meeting on
the Molecular Basis of ME/CFS was capped off by a Community Symposium
at Stanford University. It was the second annual meeting of its kind
built upon the success of the year before with the working group
meeting stretching out an extra day beyond its predecessor. The
quantity of contributing researchers was impressive, but the quality
of the research was particularly inspiring.

The message of the year before was about trying to accumulate as much
information as possible, to gather the puzzle pieces. This year the
puzzle pieces have begun to be resolved with the next challenge to
determine how they fit together.

The Community symposium began with a welcome from Linda Tannenbaum,
OMF Founder and CEO/President, greetings from Janet Dafoe, patient
liaison, and opening remarks by Ron Davis, symposium chair.

The talks began with Dr. Raeka Aiyar, the Symposium moderator, who now
works for the New York Stem Cell Foundation (NYSCF). Stem cell
applications for research is an area that Dr. Aiyar believes has the
potential for helping understand ME/CFS and to find treatments.

Dr. Oystein Fluge gave the Keynote Address. Unable to provide specific
details about the recent Rituximab trial, Dr. Fluge went on to
elaborate on previous studies of metabolism on ME/CFS patients and
other prospective clinical trials that are underway. Their lab is
uniquely set up to allow interaction between clinical trials and
observational research with both areas concurrently informing the

The current clinical trial Dr. Fluge is working on is CycloMe, an
open-label phase 2 trial looking at the effect of cyclophosphamide on
ME/CFS patients. "The results are interesting!" However, more details
are not able to be shared until publication.

The central point of their metabolism studies is that it is consistent
with several other publications from other researchers. The additional
information they provide is an inhibited pyruvate dehydrogenase
complex (PDH), an enzyme that enables the entry of sugar breakdown
products to enter the mitochondria (the powerhouse of the cell).
Interestingly, this enzyme is a central energy metabolism control
point that can determine if sugar is largely used for energy
production or if amino acids and fatty acids are being utilised
instead. The latter seems to be the consensus findings across research

Dr. Wenzhong Xiao unloads a wealth of findings from the Severely Ill
Patient Study (SIPS) he heads up at Stanford. Sleep monitoring
determined several alterations compared to healthy controls, while
morning cortisol levels were also attenuated. Together this indicates
a significant impact to the sleep/wake cycle of people with ME/CFS.
Viral pathogens have long been tied to ME/CFS with no consistent
findings. Dr. Xiao described an extensive virus search that found no
significant difference in viral pathogens between patients and
controls. The study of the microbiome revealed variations in the
bacteria of the gut, and interestingly, a neuroprotective metabolite
(3-Indolepropionate) produced by gut bacteria appears to be
significantly reduced in ME/CFS patients.

Dr. Xiao caps off his findings by displaying an integrative web of all
associated data points from the SIPS study connected to the central
diagnosis of ME/CFS. The hope is to add the data from other studies to
discover if the connected associations continue to hold.

Next up is Dr. Jonas Bergquist discussing his new study looking at
peptides and protein markers in the cerebrospinal fluid (CSF) from
ME/CFS patients, Multiple Sclerosis (MS) patients and healthy
controls. He reveals preliminary data from the study that show
elevations of protein markers indicative of neuroinflammation, cell
damage and repair in ME/CFS, and significant differences are observed
between MS and ME/CFS patients.

Secondly, Dr. Berquist screens for steroid levels and has found a
decrease of pregnenolone with non-significant downregulation of most
other steroids. Pregnenolone is a neurosteroid produced in the

Thirdly, Adrenergic and Muscarinic receptor autoantibodies were
significantly elevated in plasma from ME/CFS, and this has now been
observed in two separate studies. Importantly, no such autoantibody
changes were found in the CSF.

Dr. Alain Moreau is looking into the role of circulating microRNA in
ME/CFS. MicroRNA are small molecules that circulate throughout the
body and can regulate the production of proteins and enzymes from
genes. He hypothesizes that "ME/CFS is caused by a disturbance in the
expression of microRNAs, which modulate immune functions, energy
metabolism and physiological stress response". Dr. Moreau uses a
massager arm cuff to stimulate a reaction in ME/CFS patients, a simile
to post-exertional malaise. He measures the microRNA before and after
this stimulation and measures the alteration that occurs in ME/CFS as
compared to controls. Significant variations occur between ME/CFS and
controls. Furthermore, the data is able to be split into 4 subtypes
based on the microRNA, which relates to variations in symptom

Dr. Maureen Hanson follows in a similar vein to Dr. Moreau by looking
at studying ME/CFS patients before and after an exercise challenge to
compare the dynamic response of ME/CFS patients as compared to healthy
controls. This study will focus on metabolite, gene expression and
cytokines. Similarly, a second study looking at ME/CFS patients on
Ampligen will look at symptom changes over time in conjunction with
changes in metabolites, gene expression and cytokines.

Dr. Hanson also reports on a new metabolomics study looking at ME/CFS
compared to controls. The findings align nicely with previous studies,
and upon analyzing data across other studies in the field, there were
no separate sub-groups identifiable based on the metabolites.

Dr. Ron Tompkins begins by talking about the initiation of the ME/CFS
Collaborative Research Center at Harvard (which Dr. Davis 
affectionately calls the "Stanford of the East")
. Dr. Tompkins professes his embarrassment as a Doctor by the way his community
generally responds to a disease they don't understand. Dr. Tompkins
has spent a lot of time researching the impact of significant trauma
on the body that was significant enough to kill you (a 20% mortality
rate). Through these studies he has a strong working knowledge on the
interplay of inflammation, immunity and metabolism.

The initial research they aim to begin is a thorough understanding of
muscle recovery with a multi-omic exploration of muscle biopsies from
ME/CFS patients, the first study of its kind. They also wish to begin
functional neuroimaging studies. The focus seems to be on
understanding the differences in tissues of the body as distinct from
blood plasma and immune cells.

With enhanced funding, the Research Center at Harvard would be ideal
for a setup of clinical trials to fast-track promising and potential
treatments for ME/CFS.

Michael Sikora is a graduate student under Lars Steinmetz, professor
of genetics and member of the Stanford Genome Technology Center who
are collaborating with Mark Davis. He has been working to establish
the role of T cells and the immune system in ME/CFS. They have found
the significant increase in T cells in ME/CFS patient compared to
controls indicating an activated immune response. Furthermore, the T
cell expansion signature appears distinct in ME/CFS from other
diseases like Multiple Sclerosis and Lyme disease where immune
activation is also present. Currently, they are focusing on the cause
for the immune activation, whether it's in response to an infection or
in response to self (autoimmunity).

Dr. Jarred Younger discusses his recent research on neuroinflammation.
Using a similar technique to an MRI, Dr. Younger can evaluate the
levels of metabolites in sections of the brain. Lactate is a
metabolite found as the product of sugar breakdown for energy
production (known as the process of glycolysis). Lactate was found to
be elevated in areas of the brain that are responsible for the
sickness response. "This is exactly what would happen if ME/CFS was a neuroinflammatory disorder", Dr. Younger explained. The method used
also enables the prediction of temperature in the brain, and
temperature increase is apparent in the brain of ME/CFS patients.

The same regions of the brain in which Dr. Younger had found
elevations in lactate and temperature indicative of neuroinflammation
were also previously observed to have activated microglia, which are
consistent with neuroinflammation.

Dr. Ron Davis discusses the search for biomarkers with a particular
focus on three new technologies being developed to find differences
between ME/CFS and healthy controls. First, he reintroduces the
impedance test as a marker for ME/CFS. The addition of salt to ME/CFS
and control plasma was enough to produce a significant alteration in
the ME/CFS impedance signal as opposed to the control signal. Second,
new technology produced in conjunction with San Jose State University
looks to assess red blood cell deformability in ME/CFS patients by
evaluating the speed of transit through a tiny capillary. They have
found that ME/CFS cells are significantly less deformable than healthy
cells. Finally, magnetic levitation of cells shows that ME/CFS white
blood cells are lighter than those of healthy controls. All these
instruments effectively separate ME/CFS and control plasma, red blood
cells or white cells, and each is fabricated for a very low cost. It's
possible to create a device that combines these methods of detection
to enhance specificity. All these instruments in conjunction with
metabolite tests from Dr. Robert Naviaux and Dr. Robert Phair will be
compared in a "bake-off" to determine the most effective diagnostic
for ME/CFS. The key for a successful diagnostic is that it accurately
identifies illness (low false positives and false negatives, is easy
to produce and simple enough to perform that it may be usable

Dr. Robert Phair is now known as the "metabolic trap guy". He comes
from a background of engineering and physiology and hopes to apply
systems engineering to human physiology. His focus is on modeling of
complex metabolic systems, with a corrent focus on substrate
inhibiting enzymes.

He emphasizes that the outbreaks of ME/CFS were a particularly
important clue to him that suggested that any genetic component
related to the illness would likely be common.

He discusses non-linear system theory as important for biology but
especially important in explaining some of the confounding elements of
ME/CFS. His hypothesis began with identifying areas of metabolism that
could form bi-stability, two steady states that can be entered into
that are functionally distinct from each other, one healthy and one

First he found mutations in a gene called IDO2. IDO2 is an enzyme that
converts tryptophan (an essential amino acid) to kynurinine.
Tryptophan is also processed to seratonin. IDO2 is one of two enzymes
that process tryptophan, the other being IDO1. These two enzymes seem
to do identical things, but it's actually more complicated. At lower
levels of tryptophan, IDO1 converts tryptophan to kynurenine, but IDO2
is inactive. But IDO1 is a substrate-inhibited enzyme whereby too much
tryptophan in a cell stops its function, causing tryptophan to no
longer be processed and build up its levels in the cell. At these high
levels of tryptophan, IDO2 takes over the processing of tryptophan.
However, all the ME/CFS patients in the SIPS cohort had mutations in
IDO2 making it non-functional. Without IDO2 there is essentially a
block created that stops tryptophan converting to kynurenine and could
force it through to serotonin.

Flux experiments were initiated to measure the levels of tryptophan
and kynurenine in ME/CFS white blood cells; these showed that
tryptophan is higher and kynurenine is lower than in healthy controls,
consistent with the existence of a metabolic trap in the patients
tested. These experiments have only been conducted on 6 ME/CFS
patients and 6 healthy controls so far, and more patients will be
tested as fast as possible.

Dr. Ron Davis closes the symposium by explaining the importance of Dr.
Phair's findings but also warns about cherry-picking of data to
support a hypothesis. Good science is accomplished by forming a
testable hypothesis that makes specific predictions and doing
experiments to see if those predictions obtain. This work is still at
the beginning and will require much more exploration to determine
whether it is definitive of ME/CFS. Dr. Davis also emphasizes the need for funding at the present time. To any big donors out there, he urged, "This is the time to donate, as we may be on the precipice of a crucial finding for the illness." Dr. Davis then explained how
fundamental these pathways are to the control of a person's
biochemistry, and that It's exceptionally dangerous to begin
experimenting on one's self without more information.
Self-experimentation could have dire consequences. Dr. Davis implores
the patients to be patient.

In summary, Dr. Davis states: "A lot of progress has been made in the
last year. There is a lot more data and it is now generating testable
hypotheses. More exciting collaborations are being established.
Excellent new people are entering the field. The future is looking
even more hopeful. Our partnership with OMF has been instrumental for
this progress and for the support of this symposium. We are now on the
brink of even more exciting progress, but as always, funding is the
rate-limiting step. Now is a crucial time to donate to accelerate the

Tuesday, October 23, 2018

NIH Funding Down for 2018

NIH Funding for ME Goes Down in 2018

Posted on October 21, 2018 by Jennie Spotila


Fiscal year 2018 is over, so now we can answer the question of whether
ME research funding at NIH would go up or down. As I predicted back in
July, the answer is down.

Here's the TL;DR version:

- NIH funding for ME research decreased 17% in 2018.
- Funding for non-Center grants will decrease an additional 30% in
2019 unless NIH funds enough new grants to replace the expired ones.
- NIH's funding is now heavily concentrated at a small number of institutions.
- NIH's ancillary activities are not sufficient to overcome the funding problem.
- Some of the most important contributors are missing in action.
NIH must stop blaming people with ME for the low number of research
- Given that NIH funding has decreased, how should we respond?